1. Field of the Invention
The invention relates to optical and electronic devices and to methods for fabricating such devices.
2. Discussion of the Related Art
Recent developments have provided a number of techniques for custom fabricating structures with feature-sizes and feature-separations on the order of a nanometer (nm). The techniques use deoxyribonucleic acid (DNA) tiles to produce structures with such small feature-dimensions. Several articles describe methods for fabricating DNA tiles and larger structures made of DNA tiles. These articles include: “Design and self-assembly of two-dimensional DNA crystals” by Erik Winfree et al, Nature, vol. 394 (1998) pages 539-544; “DNA-Templated Self-Assembly of Protein Arrays and Highly Conductive Nanowires” by Hao Yan et al, Science, vol. 301 (2003) pages 1882-1884 (Herein, referred to as Yan1.); and “DNA-Templated Self-Assembly of Protein Arrays and Highly Conductive Nanowires, Supporting Online Material” by Hao Yan et al, published online at www.Sciencemag.org, Science, vol. 301 (September 2003) 12 pages (Herein, referred to as Yan2.). The three above-listed publications are incorporated herein by reference in their entirety.
FIG. 1 shows a planar DNA structure 10 that can be made from exemplary DNA tiles 12. The exemplary DNA tiles 12 are shaped like crosses. The crosses have several arms 14, and each arm 14 includes more than two strands of DNA.
FIG. 2 shows nucleotide base sequences for nine single-stranded artificial DNA oligomers, i.e., SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, and 9, that hybridize together to form the exemplary DNA tiles 12 of FIG. 1. In the base sequences, ** indicates the “5” end of the DNA backbone, and a, t, c, and g indicate the respective bases adenine, thymine, cytosine, and guanine. DNA tiles can be made from DNA oligomers with other nucleotide base sequences, e.g., nine DNA oligomers obtained by reversing each nucleotide base sequence of FIG. 2.
During formation of the exemplary DNA tile 12, sixteen nucleotide base subsequences of the DNA oligomers shown in SEQ. ID. Nos. SEQ ID NOs: 1-9 hybridize to complementary nucleotide base subsequences. After formation, the exemplary DNA tiles 12 have unhybridized “t t t t” sequences. The exemplary DNA tiles 12 also have other short unhybridized base sequences r, r*, s, s*, v, v*, w, w* located at lateral edges of the DNA tile 12, i.e., at ends of the cross. Herein, the asterisk “*” indicates a complementary base sequence. The short sequences at the lateral edges of each DNA tile 12 have about 3-5.
Herein, such short unhybridized nucleotide base sequences at the edges of DNA tiles will be referred to as sticky ends. While sticky ends do not hybridize in single DNA tiles, they can hybridize between different DNA tiles to produce larger structures from the DNA tiles, e.g., planar DNA structure 10.
One method for forming planar DNA structure 10 involves performing the following steps. First, an aqueous solution of DNA oligomers is prepared at a temperature of about 80° C.-90° C., e.g., a solution of DNA oligomers defined by SEQ ID NOs: 1-9. In the solution, the DNA oligomers for making a tile have equal molar concentrations. The solution includes, e.g., the buffer Tris to maintain the pH at about 7.6 and also includes suitable amounts of EDTA and magnesium acetate for DNA hybridization. Second, the solution is slowly cooled to room temperature at a cooling rate of about 1 degree centigrade per 1-15 minutes. During early portions of the cooling process, complementary nucleotide base sequences of the DNA oligomers, e.g., DNA oligomers with SEQ ID NOs: 1-9, hybridize with complementary base sequences to form the DNA tiles. During the early part of the cooling, thermal excitations upset weak bonds that may form when the short base sequences of the sticky ends hybridize between different DNA tiles. For that reason, the formation of DNA tiles typically occurs prior to substantial joining of the different DNA tiles. At later parts of the cooling process, the lower temperatures enable the short sticky ends to stably hybridize thereby joining together different DNA tiles, e.g., to form the tiled planar DNA structure 10.
Modifying the individual DNA tiles enables one to predetermine the global form of the structure that will form when the DNA tiles hybridize together. By using a mixture of DNA tiles with different sticky ends, one can predetermine both the size and the shape of final tiled structure. When such mixtures of DNA tiles are used, the above-described method is modified so that the different types of DNA tiles are fabricated separately. Separate fabrication avoids undesired hybridizations between the DNA oligomers for the different types of tiles, i.e., DNA oligomers that different by subsequences for sticky ends. After forming the DNA tiles, the solutions of the different types of DNA tiles are combined and further cooled to produce the desired tiled DNA structure, e.g., planar DNA structure 10.
Referring to FIG. 3, configuration 11 illustrates how control over the global form of a tiled DNA structure can result when different types of DNA tiles 12′ are hybridized together. Here, DNA tiles 12′ have six different combinations of sticky ends. The combinations of sticky ends were selected to ensure that hybridization of the DNA tiles 12 would produce a rectangle having a length to width ratio of 3:2. In particular, while the DNA tiles 12′ have complementary pairs of sticky ends (δ, δ*), (∈, ∈*), (μ, μ*), (ν, ν*), (γ, γ*), (α, α*), (β, β), (γ, γ*), other pairings of DNA sticky sequences δ, δ*, ∈, ∈*, μ, μ*, ν, ν*, γ, γ*, α, α*, β, β*, γ, γ*, and κ do not stably hybridize. For that reason, the different DNA tiles 12′ of FIG. 3 will form a single stable configuration, i.e., a 2×3 rectangle, in response to being combined and enabled to hybridize.
Other methods are known for making planar DNA structures with preselected shapes from fewer types of DNA tiles, i.e., fewer combinations of sticky edges. These other methods, e.g., enable the formation of rectangular DNA sheets having various lengths and widths. These methods are, e.g., described in “Self-Assembled Circuit Patterns” by Matthew Cook et al, DNA Computers 9, LNCS, vol. 2943 (2004) pages 91-107; and “Algorithmic Self-Assembly of DNA Serpinsky Triangles” by Paul W. K. Rothemund et al, PloS Biology, vol. 2, issue 12 (2004) pages 2041-2053. Both of the above-listed articles are incorporated herein by reference in their entirety.
A variety of methods are also available for functionalizing individual DNA tiles to bind metal particles.
A first such method involves hybridizing DNA oligomers of FIG. 2, i.e., SEQ. ID. Nos. 1-8, with a new DNA oligomer to form biotin-functionalized DNA tiles and then, binding a gold-labeled protein to these biotin-functionalized DNA tiles. In this method, the new DNA oligomer has the same base sequence as the remaining DNA oligomer of FIG. 2, i.e., SEQ. ID. No. 9, except that one of the unhybridized “t t t t” subsequences is replaced by a “t t biotin t t” subsequence. That is, the new DNA oligomer includes the protein biotin bond to a thymine base. The biotin will bind other proteins such as streptavidin and avidin. When the biotin-functionalized DNA tiles are mixed in solution with gold-labeled streptavidin or gold-labeled avidin, the biotin causes the particles of gold particle to be bound to the DNA tiles. Gold-labeled streptavidin is sold by Molecular Probes, Inc., 29851 Willow Creek Road, Eugene, Oreg. 97402 USA (www.probes.com). Relevant products are catalog numbers A32360 and A32361 for the ALEXA FLUOR® 488 streptavidin colloidal gold conjugates and catalog numbers A24926 and A24927 for the ALEXA FLUOR® 488 and 595 FLUORNANOGOLD™ conjugates with gold particles. Gold-labeled avidin is available from Sigma-Genosys, 1442 Lake Front Circle, The Woodlands, Tex. 77380 USA (www.sigma-genosys.com).
A second such method involves functionalizing one or more of the constituent DNA oligomers with a thiol group and then, using the thiol group to chemically bind a gold particle. Methods for adding a thiol group to one end of a DNA oligomer are known to those of skill in the art. One or more of the DNA oligomers SEQ ID NOs: 1-8 of FIG. 2 may be functionalized with thiol groups prior to formation of the DNA tiles. Alternately, one of the DNA oligomers of SEQ ID NOs: 1-8 may be replaced by two shorter DNA oligomers where one of the shorter DNA oligomers is functionalized by a thiol group. After making DNA tiles with DNA oligomers functionalized by the thiol groups, gold particles are added to the solution of functionalized DNA tiles. The thiol groups will cause the gold particles to be chemically bonded to the DNA tiles.
In a third method, the DNA tiles are fabricated with an extra base sequence that does not hybridize during tile-formation. Then, complementary base sequences having attached gold particles are mixed with a solution of the formed DNA tiles. The complementary base sequences bind to the DNA tiles thereby binding the gold particles to said DNA tiles.